Your guide to making money in the multi-billion dollar marijuana industry

he health and psychological consequences of cannabis use chapter 5

National Drug Strategy
Monograph Series No. 25

5. The acute effects of cannabis intoxication
5.1 Psychological and physical effects
Any attempt to summarise the acute effects of cannabis, or of any
psychoactive drug, is necessarily an oversimplification. The effects
experienced by the user will depend upon: the dose, the mode of
administration, the user's prior experience with the drug, any
concurrent drug use, and the "set" - the user's expectations, mood
state and attitudes towards drug effects - and "setting" - the social
environment in which the drug is used (Jaffe, 1985). The following
descriptions of the typical effects of cannabis are made with this
qualification in mind.
The major motive for the widespread recreational use of cannabis is
the experience of a subjective "high", an altered state of
consciousness which is characterised by: emotional changes, such as
mild euphoria and relaxation; perceptual alterations, such as time
distortion, and; intensification of ordinary sensory experiences, such
as eating, watching films, listening to music, and engaging in sex
(Jaffe, 1985; Tart, 1970). When used in a social setting, the "high"
is often accompanied by infectious laughter, talkativeness, and
increased sociability.
Cognitive changes are usually marked during a "high". These include an
impaired short-term memory, and a loosening of associations, which
make it possible for the user to become lost in pleasant reverie and
fantasy, while making it difficult for the user to sustain
goal-directed mental activity. Motor skills, reaction time and motor
coordination are also affected, so many forms of skilled psychomotor
activity are impaired while the user is intoxicated (Jaffe, 1985).
Not all the effects of cannabis intoxication are welcomed by users.
Some users report unpleasant psychological reactions, ranging from a
feeling of anxiety to frank panic reactions, and a fear of going mad
to depressed mood (Smith, 1968; Weil, 1970; Thomas, 1993). These
effects are most often reported by naive users who are unfamiliar with
the effects of cannabis, and by some patients given THC for
therapeutic purposes. More experienced users may also report these
effects on occasion, especially after the oral ingestion of cannabis
when the effects may be more pronounced and of longer duration than
those usually experienced after smoking cannabis. These effects can
usually be successfully prevented by adequate preparation of users
about the type of effects they may experience. If these effects
develop they can be managed by reassurance and support (Smith, 1968;
Weil, 1970). Psychotic symptoms, such as delusions and hallucinations,
are very rare experiences that occur at very high doses of THC, and
perhaps in susceptible individuals at lower doses (Smith, 1968;
Thomas, 1993; Weil, 1970).
The inhalation of marijuana smoke, or the ingestion of THC, the
psychoactive derivative of cannabis, has a number of bodily effects.
Among these the most dependable are the effects on the heart and
vascular system. The most immediate effect of cannabis use by all
routes of administration is an increase in heart rate of 20-50 per
cent over baseline which occurs within a few minutes to a quarter of
an hour and lasts for up to three hours (Huber et al, 1988; Jones,
1984). Changes in blood pressure also occur which depend upon posture:
blood pressure is increased while the person is sitting, and decreases
while standing. A sudden change from a recumbent posture may produce
postural hypotension and fainting, an effect which may explain the
feeling of "light-headedness" and faintness that is often the earliest
indication of intoxication in naive users (Maykut, 1984). Increases
are also observed in the production of the catecholamine
norepinephrine, although these lag behind the cardiovascular changes,
and their mechanisms are not well understood (Hardman and Hosko,
1976).
In healthy young users these cardiovascular effects are unlikely to be
of any clinical significance. They may, however, magnify anxiety in
naive users. The cannabis-induced tachycardia and postural hypotension
may contribute to the panic attacks sometimes experienced by naive
users (Weil, 1970) who may mistakenly interpret the palpitations, and
the feeling of faintness, as symptoms of serious misadventure,
magnifying pre-existing anxiety in a positive feedback cycle that
leads to a panic attack.
5.2 Toxic dose levels
THC appears to be the component of cannabis which has the highest
direct toxicity in all animals so far tested. The toxic effects of
cannabis are mediated through its effects on neural systems. The cause
of death in experimental animals is almost invariably apnoea or
cardiac arrest, if apnoea is prevented (Rosencrantz, 1983). Due to the
development of tolerance, toxic doses depend upon the amount by which
they exceed the customary dose. In contrast to the increase in toxic
dose typical of many drugs when moving from primates to lower animals,
it appears that phylogenetically higher animals are less susceptible
to the acute toxicity of THC. Thus, the dose of THC which kills 50 per
cent of animals (LD50) when administered intravenously is 40mg/kg in
the rat but 130mg/kg in the dog and monkey (Rosencrantz, 1983).
For obvious ethical reasons there is no experimental evidence to
determine a lethal dose in humans. Nor is there any clinical evidence,
since there have been no reported cases of death attributable to
cannabis in the world medical literature (Blum, 1984; Nahas, 1984).
Extrapolation from the animal evidence suggests that the lethal human
dose of THC is at least as high as, and probably higher than, that
observed in the monkey. If this is so, then the toxic dose of THC in a
65kg adult would be 8.45kg.
A number of non-fatal toxic reactions occur in humans with higher than
normal doses. The tachycardia almost invariably produced in acute
intoxication, combined with the sensory alterations and increased
tremor commonly reported, probably contribute to the affective
components of these reactions. CNS and respiratory depression are
noted with high doses, which in severe overdose may be
life-threatening (Rosencrantz, 1983). These effects are, of course,
more dangerous to those with pre-existing cardiac irregularities.
Because of the large effective to lethal dose ratio in humans
(probably in excess of 1:1000 in non-tolerant users) the risk of
experiencing severe toxic effects of cannabis is limited by the
aversive psychotropic effects of high doses, which usually lead to
cessation of use before the onset of dangerous physical consequences.
5.3 Tolerance to acute effects
In animals, tolerance develops to the lethal, hypothermic and some of
the behavioural effects of cannabinoids. This has been attributed to
functional or pharmacodynamic adaptations of the CNS rather than to a
more rapid metabolic disposition (Jaffe, 1985). Laboratory studies in
humans involving daily dosing at high levels over periods of weeks
have demonstrated tolerance to mood effects, tachycardia, decrease in
skin temperature, increased body temperature, and impaired performance
on psychomotor tests. Abrupt discontinuation in these studies usually
produces a mild withdrawal syndrome (see below pp111-113).
5.4 Psychomotor effects
A major societal concern about cannabis intoxication is its potential
to impair psychomotor performance in ways which may directly affect
the well-being of non-users of cannabis. The prototype outcome is an
automobile accident caused by a cannabis user driving while
intoxicated. It is well known that individuals who drive while
intoxicated with alcohol are dangerous to others in proportion to
their level of intoxication. Is there evidence that intoxication with
cannabis produces impaired psychomotor performance of a nature and
degree sufficient to warrant restrictions upon its use by automobile
drivers? To what extent has cannabis intoxication contributed to road
accidents?
Psychoactive substances typically have both acute and chronic effects
on performance of a variety of tasks. Given the fact that most tasks
of interest to researchers require effort and concentration, only
those substances which enhance these very general abilities typically
improve performance. Recreational drugs are usually valued for effects
which remove the user from mundane concerns, produce relaxation, and
enhance experiences which would normally interfere with concentration
on a skilled task. Consequently, many societies enact restrictions on
the use of such drugs, either during specific tasks such as motor
vehicle driving, or at any time, as is the case with cannabis in most
Western societies, and with alcohol in many Islamic societies.
The subjective effects of cannabis include feelings of well-being and
relaxation, and sensory and temporal distortions which might be
expected to decrease performance in situations where perceptual
accuracy and attention are important. In deciding whether the
recreational use of cannabis presents a danger to the user and others
we need to consider two things: (1) the extent to which its use
disrupts the performance of potentially dangerous tasks such as motor
vehicle driving or the operation of machinery, and (2) the effect that
the drug has on the user's compliance with restrictions upon its use.
The second point refers to any disinhibitory effects of the drug which
might predispose users to ignore prohibitions on driving, or may
increase their willingness to take risks while intoxicated.
The risks of cannabis intoxication and driving will be assessed in the
following way. First, laboratory evidence on the effects of cannabis
on various psychomotor tasks will be reviewed. In the following review
of this evidence, when a number of studies have produced similar
results, only the most typical studies will be cited. (For a more
complete review of such studies see Chait and Pierri, 1992). Second,
the possible mechanisms of the psychomotor effects of cannabis will be
briefly discussed. Third, the literature on the effects of cannabis on
performance in driving and flying simulators will be briefly reviewed.
Fourth, the experimental literature on the effects of cannabis
intoxication on on-road driving will be reviewed. Finally, the limited
epidemiological evidence on the contribution of cannabis to motor
vehicle accidents will be considered.
5.4.1 Effects of cannabis on psychomotor tasks
Muscle control. Standing steadiness (Kiplinger et al, 1971) and hand
steadiness (Klonoff et al, 1973) are both adversely affected by
cannabis. Finger or toe tapping speed does not appear to be reliably
affected (Weckowicz et al, 1975; Evans et al, 1976; Milstein et al,
1975; Dalton et al, 1975), as only one study (Klonoff et al, 1973)
found a decrement in finger tapping.
Reaction time. Simple reaction time does not appear to be reliably
affected by cannabis. Some studies have reported decrements in mean
reaction time (Borg et al, 1975; Dornbush et al, 1971), or the
variability of reaction time (Braden et al, 1974), while others have
found no difference (Evans et al, 1973). Choice reaction time tasks,
in which the response is conditional not only upon the occurrence of a
stimulus, but also the presence of some other discriminant (such as
the pitch of a tone or the colour of a visual stimulus), have been
administered to determine the effect of cannabis. In a number of these
studies, reaction time was indeed slower after cannabis use (Borg et
al, 1975; Block & Wittenborn, 1984; 1986), although there were some
studies which found no change (Peeke et al, 1976; Block & Wittenborn,
1984). With only one exception (Low et al, 1973), errors in choice
reaction time were not increased by cannabis.
Single tasks of manual dexterity. Pursuit rotor tasks, in which the
subject attempts to follow a rotating target with a pointer, are
generally performed worse after cannabis use (Manno et al, 1971; Manno
et al, 1970), although studies employing regular users (Salvendy &
McCabe, 1975; Carlin et al, 1972) have found no effect, suggesting
that the regular users developed tolerance to the effects of cannabis.
Other tracking tasks are generally not affected (Zacny & Chait, 1991;
Heishman et al, 1989). Tests in which the subject must manipulate and
accurately place small items (Dalton et al, 1975; 1976; Evans et al,
1973) are usually affected, while sorting tasks may (Chait et al,
1985) or may not (Kelly et al, 1990) be performed less well.
Concurrent tasks. Most concurrent task studies use one task which
requires almost continuous attention, typically tracking, and one in
which significant stimuli occur sporadically, often within a larger
number of non-significant stimuli. The tasks are often referred to as
the central and peripheral tasks respectively. The performance of
concurrent tasks is almost always affected negatively by cannabis,
although the effects on the component tasks are not consistent. Number
or proportion of peripheral targets missed (MacAvoy & Marks, 1975;
Marks & MacAvoy, 1989; Casswell & Marks, 1973; Moskowitz et al, 1972),
proportion of hits (Moskowitz, Sharma & McGlothlin, 1972), false
alarms (Chait et al, 1988, MacAvoy & Marks, 1975; Moskowitz &
McGlothlin, 1974) or reaction time to peripheral targets (Perez-Reyes
et al, 1988; Evans et al, 1976; Moskowitz et al, 1976) may suffer, but
no interpretable pattern of decrements has emerged. It may be the case
that while overall performance on concurrent tasks is decreased during
cannabis intoxication, differences in the tasks used produce various
patterns of effect. While there has been some speculation as to
whether the effects of cannabis in concurrent tasks might be
concentrated on the central or peripheral tasks (Moskowitz, 1985), no
observed pattern has emerged to clearly support these conjectures.
5.4.2 Possible mechanisms of psychomotor effects
Sensory disturbances. Reports of the subjective experience of cannabis
intoxication include altered experience in all sensory modalities, as
well as in the perception of space and time (Tart, 1970). Since almost
all tasks of psychomotor performance include important visual and
auditory components, sensory disturbances might well affect the
ability to perform such tasks. Studies of the ability to discover
embedded figures within complex designs have shown that this is
impaired by cannabis (Carlin et al, 1972; Carlin et al, 1974; Pearl et
al, 1973). Performance decrements due to cannabis in the Stroop colour
naming test have been reported (Carlin et al, 1972; 1974), although it
is not clear whether disturbed perception has any significant effect
upon this task.
Central Nervous System depression. Both the toxic and behavioural
effects of cannabis indicate that it acts as a CNS depressant, at
least in moderate to high doses. It might seem reasonable to
hypothesise that this general effect might contribute to slowed
reaction times, inability to maintain concentration, and lapses in
attention. This is certainly the case with alcohol and other CNS
depressants. When compared to the relatively large and reliable
depressant effects of moderate doses of alcohol, it is clear that this
effect of cannabis is not the primary mediator of performance changes.
It must be stressed, however, that high doses of cannabis would make
this aspect of its action on psychomotor skills more important.
Motivational changes. A great deal has been written about the supposed
effects of cannabis on human motivation. Hypotheses concerning the
motivational effects of chronic cannabis use have been reviewed
separately (see chapter 7.2). Cannabis users routinely report reduced
desire for physical activity and increased difficulty of concentrating
on intellectually demanding tasks such as reading for study (Tart,
1970). Studies designed to test the effect of cannabis on the
willingness to perform laboratory "work" have found no striking
decrements (Mendelson, 1983). This is consistent with comparisons of
manual workers who used cannabis with those who did not (Rubin &
Comitas, 1975; Stefanis et al, 1977). Indeed, the counter-argument
that cannabis users can voluntarily compensate for some of the
impairing effects of the drug has received experimental support
(Cappell & Pliner, 1973; Robbe & O'Hanlon, 1993). As discussed below,
motivational changes are surely important in decisions made outside
the laboratory, but there appears to be no reliable evidence that
motivational changes are responsible for any major proportion of the
psychomotor effects of cannabis.
5.4.3 Effects of cannabis on simulated driving and flying
Simulated driving tasks. As the previous sections have shown, there is
considerable evidence that cannabis intoxication has some negative
effects upon performance which become more pronounced with increasing
task difficulty. Motor vehicle driving is a complex task, especially
in conditions of heavy traffic or poor road or weather conditions, and
as such, it might be expected to be adversely affected by cannabis.
Simulated driving tasks require skills which are similar to those
involved in driving, which can be performed under controlled
laboratory conditions. When special efforts are made to simulate the
performance characteristics of a car, simulations have two major
advantages (Smiley, 1986). First, cannabis users an be tested after
taking doses of cannabis which it would be unethical to use on the
road. Second, they can be placed in simulated emergency situations
which test their level of impairment in ways that would be
impermissible on the road. The disadvantage of simulator studies
derives from the difficulty of achieving sufficient fidelity to
on-road driving tasks.
One of the earliest studies by Crancer et al, (1969) found only that
"speedometer errors" increased in simulated driving after cannabis
use. In one of the more influential studies, Dott (1972) reported an
apparent decrease in the willingness to take risks in simulated
passing of another vehicle after cannabis use, while alcohol had the
opposite effect. Alcohol also tended to hamper the subjects' response
to stimuli signalling an emergency condition, while cannabis had
little effect on this response. Both, however, increased reaction time
to a more routine signal. A similar dissociation of the effects of
alcohol and cannabis was reported by Ellingstad, et al, (1973) who
found that cannabis did not appear to increase risk-taking, whereas
alcohol did. Cannabis affected the ability to judge the time taken to
pass another vehicle, while alcohol did not. Moskowitz et al (1976)
found that alcohol altered the visual search patterns of subjects
performing a simulated driving task, while cannabis did not. The
alterations found with alcohol were, in theory, consistent with a
reduced ability to scan for hazardous events, but no reliable
difference in task performance was found with either drug.
Smiley (1986) critically reviewed the research on the effects of
cannabis intoxication on simulated driving. She argued that the
earlier studies which showed fewer effects on car control than later
studies suffered because of their unrealistic car dynamics. Later
studies which used driving simulators with more realistic car dynamics
have shown impairments of lane control after cannabis use. Some of the
studies have also shown reductions in risk-taking as manifested in
slower speeds, and maintenance of a larger distance from the car in
front in following tasks (Smiley, 1986).
Simulated flying. Janowsky et al (1976) found substantial increases in
the number and magnitude of errors during a simulated flight after
taking cannabis. These were principally in keeping the plane at the
proper altitude and heading. Yesavage et al (1985) originally reported
negative effects of cannabis on some components of a simulated flying
task up to 24 hours after smoking, but this study did not include a
control group. A later study (Leirer et al, 1989) which attempted to
replicate this result with a control group found only an effect one to
four hours after smoking. A third study which also included a control
group (Leirer et al, 1991) again demonstrated decrements in the
composite performance score up to 24 hours after smoking cannabis.
Much has been made of these findings by critics of cannabis use, but
the effects are very small and of uncertain significance for flying
safety. Jones (1987) has argued that the use of cannabis by pilots in
the 24 hours preceding flying may be more an indicator of poor
judgment, rather than a cause for concern about the residual
psychomotor effects of cannabis.
5.4.4 Effects of cannabis on on-road driving
It is often remarked that the activity most often cited as dangerous
when performed under the influence of recreational drugs - motor
vehicle driving - is one of the least studied. Given the concern about
the safety of the experimental subject in drug and driving
experimentation, it is understandable that such studies have been
relatively uncommon. A review by Nichols (1971) found that there were
no well controlled observations of the effects of cannabis on driving
performance. This situation changed with research commissioned by the
Canadian Commission of Inquiry into the Non-Medical use of Drugs. A
comprehensive report published by Hansteen et al (1976) showed that a
moderate dose of alcohol (approximately 0.07 BAC) or THC (5.9mg)
impaired driving on a traffic-free course (as measured by the number
of times the lane-defining cones ("witch's hats") were struck).
Driving speed was decreased after cannabis but not after alcohol use.
Smiley et al (1975), using a different type of course, found that
reaction time to signal stimuli was increased with the combination of
cannabis and alcohol. Klonoff (1974) studied driving on a closed
course, and in city traffic, after a placebo and two doses of smoked
cannabis (4.9mg and 8.4mg THC). Closed course driving was scored by
the number of cones hit on a precisely laid out path. Driving in
traffic was scored by observation of eleven categories of driving
skill, similar to those used in some driving tests. Driving on the
closed course was impaired by both doses, as indicated by a higher
proportion of subjects whose performance declined after cannabis use.
Driving in traffic, however, while showing a trend toward poorer
performance, was not significantly affected, and the effects of
cannabis were much more variable. Sutton (1983) also found that
cannabis had little effect on actual driving performance. Peck et al
(1986) recorded performance on a range of driving tasks on a closed
circuit on four occasions after the administration of placebo, up to
19mg of smoked THC, 0.84g/kg of alcohol, and the combination of both
drugs. On most individual and derived composite measures, cannabis
impaired performance. This study is important in that there was a high
degree of concordance between objective performance measures (e.g.
number of traffic markers hit during manoeuvres), subjective estimates
of performance by the drivers, and ratings by police observers.
However, the conclusion reached was that the effects of cannabis on
driving performance were somewhat less than those of alcohol. Robbe
and O'Hanlon (1993), have reported the methodology, but not the
detailed results, of a study of driving in traffic. Their brief report
suggests that their results also indicated little impairment of actual
driving skills after cannabis. They speculated that since drivers were
aware of their intoxication, they had successfully attempted to
counter the impairment.
Overall, the effects of cannabis use on on-road driving have been
smaller than the comparable effects of intoxicating doses of alcohol
in the same settings (Smiley, 1986). The most consistent cannabis
effect has been that drivers reduce their risk by slowing down; a
finding that contrasts with the consistent finding that subjects
typically increase their speed when intoxicated with alcohol. It is
probably this compensatory behaviour by cannabis users that explains
the comparatively small effects of cannabis intoxication in on road
studies. For ethical reasons such studies have not been able to
adequately test the response of cannabis intoxicated drivers to
situations that require emergency decision, in which there is less
opportunity to compensate for impairment. The few studies which have
attempted to simulate this situation (e.g. by using subsidiary
reaction tasks in addition to driving) have shown that cannabis
intoxication impairs emergency decision-making (Smiley, 1986).
The small effects of cannabis on driving performance seem at odds with
its effects on laboratory tasks requiring divided attention. Peck et
al (1986) have pointed out, however, that the subtle performance
effects of drugs in laboratory divided attention tasks may be poor
predictors of driving performance. While the combination of
performance abilities which is tapped by the typical divided attention
task, such as concurrent pursuit tracking and visual discrimination,
is plausibly related to driving, the tracking task is usually a much
more difficult task than driving under normal conditions. Much more
attention must be allocated to the central task in most divided
attention tests, for example, leading to a substantial decrease in
performance when drugs such as cannabis are taken. In addition, in the
laboratory the subject is unable to vary a key task parameter, such as
driving speed, in order to compensate for any perceived impairment.
Hence, while laboratory divided attention tasks may be ideal for
detecting small drug effects, they may over-estimate the effects of
drugs on actual driving. It is not surprising then that many studies
which have used both types of test have reported less effect on actual
driving than on laboratory tasks or simulated driving.
5.4.5 Studies of cannabis use and accident risk
While cannabis produces decrements in psychomotor performance in
laboratory and controlled settings, it does not necessarily follow
that these decrements will increase the risk of being involved in
accidents. It may be, for example, that cannabis users are less likely
to drive than drinkers because they are more aware of their
intoxication. The survey evidence suggests that this is not the case.
Several surveys (e.g. Dalton et al, 1975; Thompson, 1975; Klonoff,
1974; Robbe & O'Hanlon, 1993) have found that cannabis users are
generally aware that their driving is impaired after using cannabis
but the majority had driven, or would drive, after using cannabis,
despite this recognition of impairment (Klonoff, 1974). This finding
is consistent with observations on the recreational use of alcohol
when driving (Smart, 1974).
Even if cannabis users drive when intoxicated it does not necessarily
follow that they will be over-represented among drivers involved in
accidents. It could be, for example, that cannabis users take special
care and avoid risk-taking when driving while intoxicated. This
possibility is difficult to investigate because there have been no
controlled epidemiological studies conducted to establish whether
cannabis users are at increased risk of being involved in motor
vehicle or other accidents. This is in contrast to the instance of
alcohol use and accidents, where case-control studies have shown that
persons with blood alcohol levels indicative of intoxication are
over-represented among accident victims (Holman et al, 1988).
In the case of cannabis, all that is available are studies of the
prevalence of cannabinoids in the blood of motor vehicle and other
accident victims (see McBay, 1986 for a review). Most often these have
been retrospective studies of the prevalence of cannabinoids in blood
tested post-mortem, which have found that between 4 per cent and 37
per cent of blood samples have contained cannabinoids, typically in
association with blood alcohol levels indicative of intoxication (e.g.
Cimbura et al, 1982; Mason and McBay, 1984; Williams et al, 1985).
Zimmerman et al (1983) have reported similar prevalence data on blood
cannabinoid levels among Californian motorists tested because of
suspicion of impairment by the Highway patrol. Soderstrom et al (1988)
have conducted one of the few prospective studies among trauma
patients rather than accident fatalities, which showed a high
prevalence of bloods positive for cannabinoids (35 per cent).
These studies are difficult to evaluate for a number of reasons.
First, in the absence of information on the prevalence of cannabinoids
in the blood of non-accident victims, we do not know whether persons
with cannabinoids are over-represented among accident victims
(Terhune, 1986). Although a prevalence of 35 per cent may seem high,
this is of the order of the prevalence of cannabis use among young
males who are at highest risk of involvement in motor vehicle and
other accidents (Soderstrom et al, 1988). Second, there are major
problems in using cannabinoid blood levels to determine whether a
driver or pedestrian was intoxicated with cannabis at the time of an
accident (Consensus Development Panel, 1985). The simple presence of
cannabinoids indicates only recent use, not necessarily intoxication
at the time of the accident (see above pp35-36). Third, there are also
serious problems of causal attribution, since more than 75 per cent of
drivers with cannabinoids in their blood also have blood levels
indicative of alcohol intoxication (McBay, 1986). On the basis of the
available evidence, it is accordingly difficult to draw any
conclusions about the contribution that cannabis intoxication may make
to the occurrence of motor vehicle accidents (Terhune, 1986).
One approach that has been used in an attempt to get around the
absence of data on the prevalence of cannabis use among drivers not
involved in accidents has been to perform "culpability analyses"
(Terhune, 1986). In such analyses, decisions are made as to which
drivers killed in fatal accidents are culpable (i.e. responsible for
the accident). Drivers with no alcohol or other drugs in their blood
are then used as the control group in analyses of the relationship
between the presence of drugs in blood and degree of culpability.
These studies have their problems: the culpability of the drug-free
drivers is usually high thereby reducing the ability to detect an
increase in culpability among drivers with alcohol and cannabis;
different studies use different criteria for deciding that when a
driver was intoxicated with cannabis; and as a consequence, different
studies have produced very different estimates of the relationship
between cannabinoids in blood and driver culpability (although most
have shown an increased culpability for drivers with intoxicating
levels of alcohol in their blood). As Simpson (1986) concluded after
reviewing the culpability literature: "the results are mixed and
inconclusive" (p28).
Gieringer (1988) used a different approach to circumvent the absence
of data on the prevalence of cannabinoids in drivers not involved in
accidents. He used data from a National Institute of Drug Abuse (NIDA)
household survey of drug abuse in the United States to estimate the
proportion of all drivers who might be expected to have blood and
urine samples positive for cannabinoids. On the basis of these data,
he estimated that cannabis users are two to four times more likely to
be represented among accident victims than non-cannabis users, and
that cannabis users who also used alcohol were even more likely to be
over-represented among the victims of motor vehicle accidents.
Gieringer's inference about the risks of combining alcohol and
cannabis when driving receive some support from the studies of Mason
and McBay (1984) and Williams et al (1985). Mason and McBay estimated
that at most one driver in their series of 600 drivers killed in
single-vehicle accidents was significantly impaired by cannabis use
alone, compared with between nine and 28 drivers who were impaired by
marijuana and alcohol, and 476 drivers who had blood alcohol
contentrations (BACs) greater than 0.10. Williams et al (1985)
investigated the relationship between alcohol and cannabis use and
driver responsibility for fatal accidents (as judged from police
investigations of each accident) involving young men in California.
Using the small drug-free group as the comparison, they found that
both alcohol (OR=4.7 [95 per cent CI: 2.1, 10.3]) and alcohol and
marijuana in combination (OR=8.6 [95 per cent CI: 3.3, 22.2])
significantly increased the odds of the driver being adjudged to be
responsible for the accident. Marijuana-only drivers, however, were
less likely to be adjudged responsible for their accident (OR=0.5 [95
per cent CI: 0.2, 1.3]), although numbers were small (N=19).
There is also indirect evidence that cannabis use produces an increase
in the risk of accidents, from surveys of self-reported accidents
among adolescent drug users. Two such surveys have found a
statistically significant relationship between marijuana use and
self-reported involvement in accidents, with marijuana smokers having
approximately twice the risk of being involved in accidents of
non-marijuana smokers (Hingson et al, 1982; Smart and Fejer, 1976).
More direct evidence of an association between cannabis use and
accidents is provided by two epidemiological studies, one of cannabis
use and mortality (Andreasson and Allebeck, 1990), and the other of
cannabis use and health service utilisation (Polen et al, 1993).
Andreasson and Allebeck reported a prospective study of mortality over
15 years among 50,465 Swedish military conscripts. They found an
increased risk of premature mortality among men who had smoked
cannabis 50 or more times by age 18 (RR=4.6, 95 per cent CI: 2.4,
8.5). Violent deaths were the major cause of death contributing to
this excess mortality, with 26 per cent of deaths being motor vehicle
and 7 per cent other accidents (e.g. drownings and falls). The
increased risk was no longer statistically significant (RR=1.2 [95 per
cent CI: 0.7, 1.9]) after multivariate statistical adjustment for
confounding variables such as anti-social behaviour, and alcohol and
other drug use in adolescence (Andreasson and Allebeck, 1990),
reinforcing Gieringer's suggestion that the combination of cannabis
and alcohol may be the important risk factor for accidents.
Polen et al (1993) compared health service utilisation by non-smokers
(N=450) and daily cannabis-only smokers (N=450) screened at Kaiser
Permanente Medical centres between July, 1979 and December, 1985. They
reported an increased rate of medical care utilisation by
cannabis-only smokers for respiratory conditions and accidental injury
over a one to two-year follow-up. There was also an interaction
between cannabis and alcohol use, in which cannabis users who were the
heaviest alcohol users showed the highest rates of utilisation. This
result is suggestive but minimally informative about the risks of
motor vehicle accidents, because all forms of accidental injury were
aggregated.
5.4.6 Conclusions on cannabis and driving
There is no doubt that cannabis adversely affects the performance of a
number of psychomotor tasks, an effect which is related to dose, and
which is larger, more consistent and persistent in difficult tasks
involving sustained attention. The acute effects on performance of
typical recreational doses of cannabis are similar to, if smaller
than, those of intoxicating doses of alcohol. Alcohol and cannabis
differ in their effects on the apparent willingness of intoxicated
users to take risks when driving, with persons intoxicated by cannabis
engaging in less risky behaviour than persons intoxicated by alcohol.
While cannabis produces decrements in performance under laboratory and
controlled on-road conditions, it has been difficult, for technical
and ethical reasons, to establish conclusively whether cannabis
intoxication increases the risk of involvement in motor vehicle
accidents. There is sufficient consistency and coherence in the
evidence from studies of cannabinoid levels among accident victims,
and a small number of epidemiological studies, to infer that there
probably is an increased risk of motor vehicle accidents among persons
who drive when intoxicated with cannabis. A crude estimate of the risk
is of the order of two to four times for persons driving under the
influence of cannabis. This increased risk may be largely explained by
the combined use of cannabis with intoxicating doses of alcohol.
Further research is required to elucidate this issue, although it will
not be easily resolved because of the technical obstacles to such
research. In the meantime, cannabis users should be urged not to drive
while intoxicated by cannabis, and they should be particularly warned
of the dangers of driving after combining alcohol and cannabis use.
5.5 Interactions between cannabis and other drugs
Cannabis is often taken in combination with other drugs. This is most
likely among those who use it frequently and in large quantities (Tec,
1973). The predominant drug of choice for use with cannabis is alcohol
(e.g. Carlin & Post, 1971; Hochhauser, 1977; McGlothlin et al, 1970;
Norton and Colliver, 1988) which supports the popular notion that this
combination enhances the degree of intoxication. Barbiturates, in
contrast, appear to produce an aversive intoxication when combined
with cannabis (Johnstone et al, 1975). The interactions of cannabis
with each type of drug will be considered in three ways; interactions
of toxicity, psychotropic effects and psychomotor impairment.
5.5.1 Other cannabinoids
There are slight interactions of THC with other cannabinoids found in
cannabis preparations. The two major cannabinoids other than THC which
have been extensively tested for interactions with THC and other drugs
are cannabidiol and cannabinol. Both of these compounds have been
found to have little psychoactivity when administered alone
(Hollister, 1986). In rather high doses (15-60mg), cannabidiol has
been reported to abolish the effects of 30mg of oral THC (Karniol et
al, 1975), whereas cannabinol had no apparent effect (Hollister &
Gillespie, 1975). Comparisons of smoked THC and smoked cannabis, the
latter containing the usual small amounts of cannabinol and
cannabidiol, indicate that there is, if anything, a slightly greater
psychoactive effect from the cannabis than from THC (Galanter et al,
1973; Lemberger et al, 1976). The psychotropic effects of THC also
appear to be slightly enhanced by the minor constituent cannabinoids
found in natural products when smoked (Galanter et al, 1973). No such
differences have been reported in the behavioural effects of smoked
cannabis.
5.5.2 Alcohol
Alcohol and cannabis have a number of effects in common, although the
mechanisms of these actions appear to be different. The recent
identification of the cannabinoid receptor (Howlett et al, 1990), and
an endogenous ligand for that receptor, have confirmed the hypothesis
that the central activity of cannabis is receptor-mediated (see pp
29-31 above). While the mechanism of action of alcohol is still in
question, most explanations are concerned with the effects of alcohol
upon the structure and chemistry of the cell membrane. Both drugs are
considered to be CNS depressants, especially in high doses, and both
have substantial analgesic properties. Since these effects of the two
drugs appear to be approximately additive (Siemens, 1980) it is
possible that the toxicity of high doses of Æ9-tetrahydrocannabinol
(THC) (Rosencrantz, 1983) may be potentiated by alcohol, although
there is very little evidence to support this conjecture. Neither the
metabolism of alcohol nor that of THC appears to be altered by the
presence of the other drug (Siemens & Khanna, 1977).
Alcohol and THC also appear to have similar psychotropic effects. The
perceived stimulation and euphoria at low doses are common effects, as
well as a tendency toward behavioural disinhibition over a range of
doses (Hollister & Gillespie, 1970). This interaction is generally
perceived by users as enhancing the intoxication produced by either
drug alone (Chesher et al, 1976), although contrary results have been
reported (Manno et al, 1971). However, larger doses in combination are
often reported to be aversive (Sulkowski & Vachon, 1977; Chesher et
al, 1986).
The effects of alcohol and cannabis combinations on psychomotor
performance are more complex. The majority of studies have reported
that both drugs produce impairment on a variety of psychomotor tasks,
and that the interaction is approximately additive. However, a number
of studies have reported that at low doses there is less than an
additive effect. Chesher et al (1976, 1977) found a reduction in
impairment late in intoxication after a combination of oral THC
(0.14-0.21mg/kg) and alcohol (0.5-0.6g/kg). A further study in which
the THC (0.32mg/kg) was administered one hour before the alcohol
(0.54g/kg) found no apparent antagonism (Belgrave et al, 1979).
Another study using three doses of smoked marijuana in combination
with alcohol showed a lower-than-expected impairment in the group
which received the lowest dose of THC (5mg) and the lowest dose of
alcohol (0.54g.kg) (Chesher et al, 1986). Peck et al (1986) also
reported an apparent antagonism, but only on a composite "stopping"
variable derived from driving performance. In most of their measures,
the combination of alcohol and cannabis produced additive impairments.
Siemens (1980) has proposed that alcohol may reduce the availability
of THC through a pharmacokinetic interaction demonstrated in animals
(Siemens & Khanna, 1977). Given that there is substantial evidence for
cross-tolerance between alcohol and THC (Newman et al, 1972), it is
possible that low doses of THC and alcohol in combination may enhance
the acute tolerance to alcohol (Hurst & Bagley, 1972) late in
intoxication.
5.5.3 Psychostimulants
The most characteristic effect of psychostimulants such as amphetamine
and cocaine is their activation of the sympathetic branch of the
autonomic nervous system, as indicated by increases in arousal, blood
pressure and respiratory rate. There are few actions which appear to
be common between cannabis and stimulants. The few effects on the
cardiovascular system, such as amphetamine-induced hypertension, and
THC-induced tachycardia, seem to occur independently (Zalcman et al,
1973). It is in the combined effect upon cardiac action that toxic
interactions of THC and stimulants could be dangerous, but there are
no clear indications in the literature for humans, and the evidence
from animal studies is mixed (Siemens, 1980).
The psychotropic effects of the combination of 0.14mg/kg amphetamine
and 0.05mg/kg THC have been reported as a longer and more intense
"high" (Evans et al, 1976), although a similar study using only
0.025mg/kg THC found no effect of the combination (Forney et al 1976).
While the concurrent use of cannabis and cocaine is often reported
(Miller et al, 1990), systematic study of their interaction is
lacking.
There is some evidence that amphetamine may antagonise the behavioural
impairments produced by cannabis (Zalcman et al, 1973), as a number of
stimulants appear to do in some animals (Consroe et al, 1976). The
infrequency of stimulant/cannabis combinations in recreational use
(Hollister, 1986) may be due to as yet unspecified negative
interactions experienced by users. It may be, for example, that
stimulants increase the probability of occurrence, or severity of the
acute panic reaction which sometimes occurs after cannabis use.
5.5.4 Depressants
A great deal of experimentation in animals has shown that cannabis in
general increases the depressant action of drugs such as the
barbiturates over a range of doses (Siemens, 1980). This is also the
case with oxymorphone (Johnstone et al, 1975) and diazepam (Smith &
Kulp, 1976). As with alcohol, it is likely that interactions between
these acute effects of depressant drugs would lead to the greatest
danger of acute toxicity. There is little human evidence at present,
however, to support this speculation.
The psychotropic effects produced by combinations of barbiturates with
cannabis appear to be additive (Dalton et al, 1975). As mentioned
previously, this intoxication is more likely to be aversive to the
user (Johnstone et al, 1975). The behavioural effects of the
interaction of depressant drugs with cannabis are, in almost all
reports, also additive.
5.5.5 Miscellaneous drugs
A number of other substances have been reported to antagonise various
effects of cannabis in animals, including phenitrone (Kudrin &
Davydova, 1968), pemoline (Howes, 1973) and even tamarind (Hollister,
1986). Only pemoline is acknowledged to counter the reduced motor
activity and hypoalgesia due to THC. Physostigmine has shown a complex
interaction which includes increasing the motor depression produced by
THC and antagonising the tachycardia (Freemon et al, 1975).
Propanolol, which would be expected to antagonise the tachycardia
characteristic of cannabis intoxication, also appears to abolish the
reduction in learning capacity produced by cannabis (Sulkowski et al,
1977), although an earlier study using smaller, spaced doses found no
effect (Drew et al, 1972). Recently, it has been reported that
indomethacin, a non-steroidal anti-inflammatory, reduced or eliminated
a number of physiological effects of THC, and attenuated the "high",
but did not affect the acute memory impairment (Perez-Reyes et al,
1991).
5.5.6 Conclusions on drug interactions
At present, the interactions between the effects of cannabis and other
drugs are what would be predicted from their separate actions, and are
generally relatively innocuous in recreational doses. There have been
a number of reports in which cannabis use has accompanied serious
consequences, typically when used in combination with one or more
other drugs in high doses, or over extended periods of intoxication.
However, there appears to be no evidence that cannabis is particularly
implicated in cases of heavy intoxication with other drugs. The
concurrent intoxication with alcohol and cannabis, which is the most
common combination of drugs, may have greatest relevance in motor
vehicle accidents. The separate impairments induced by the two drugs
appear to be approximately additive, and there are indications that
users of both drugs are over-represented among motor vehicle
accidents.
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